This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Integrins transmit bidirectional signals across the cell membrane through large conformational changes. Crystal structures of platelet integrin a{IIB}b3 revealed that upon binding by peptide ligands or small molecule ligand-mimetic antagonists, the integrin headpiece changes from closed to open conformation, characterized by a swing-out motion of the b subunit hybrid domain. Recently we have determined several crystal structures corresponding to transitional conformations on the pathway between closed and open headpiece, which enables us to observe the dynamics of integrin activation for the first time. Here we plan to carry out long-time molecular dynamics simulations to study how ligand induces opening of closed integrin headpiece and upon ligand dissociation what conformation the open headpiece will take.